NEW YORK (Reuters Health) - The addition of high-dose
steroids to the postoperative treatment plan for infants with
biliary atresia did not improve bile drainage in a randomized
trial conducted in the US, "although a small clinical benefit
could not be excluded," the researchers say.

"The use of corticosteroids after surgery for biliary
atresia (the Kasai surgery) is common in centers in the US and
abroad. Based on the results of the START trial, continuation of
this practice cannot be recommended," Dr. Jorge A. Bezerra, who
worked on the study and directs the Digestive Health Center at
Ohio's Cincinnati Children's Hospital Medical Center, told
Reuters Health by email.

But Dr. Mark Davenport of the Department of Pediatric
Surgery at King's College Hospital in London, UK, who wasn't
involved in the study, cautioned against concluding that
steroids are not helpful after biliary atresia surgery.

Results of the study were published online May 3 in JAMA to
coincide with a presentation at the annual meeting of the
Academic Pediatric Societies, held this year in Vancouver,
Canada.

Dr. Bezerra and colleagues note in their article that
biliary atresia is the most common cause of end-stage liver
disease in children. Hepatoportoenterostomy leads to successful
bile drainage in only about half of patients with biliary
atresia treated in the US. Controversy exists as to whether the
use of steroids after surgery improves clinical outcomes.

In the START trial, 140 infants with biliary atresia were
randomly allocated to receive IV methylprednisolone (4 mg/kg/d
for 2 weeks) and oral prednisolone (2 mg/kg/d for 2 weeks)
followed by a tapering protocol for 9 weeks or placebo started
within 72 hours of hepatoportoenterostomy.

The primary end point (powered to detect a 25% absolute
treatment difference) was defined as successful bile drainage
measured as the percentage of infants with serum total bilirubin
level <1.5 mg/dL with his or her native liver at six months
post-surgery.

The proportion of infants who met this end point was not
significantly different in the two groups (58.6% of the steroid
group vs. 48.6% of the placebo group). The adjusted absolute
risk difference was 8.7%.

Survival without liver transplantation at age 2 years (a
secondary end point) was also no different in the steroid and
placebo groups (58.7% vs. 59.4%).

Serious adverse events were common in both treatment groups
(81.4% for steroids vs. 80.0% for placebo); however, infants
treated with steroids experienced their first serious adverse
event earlier than those receiving placebo, the researchers say.

"Based on the strength of the evidence, the addition of
high-dose steroids as an adjuvant treatment for infants with
biliary atresia after hepatoportoenterostomy cannot be
recommended," the authors conclude.

In his comments on the study, Dr. Davenport told Reuters
Health, "In our field, this is an impressive machine of a trial,
bristling with macho statistical methods (Markov chain Monte
Carlo method, O'Brien-Fleming spending function). There will
probably not be another like it as BA is so rare and parents are
very suspicious of trials in babies (they could only recruit
just over half those eligible)."

However, Dr. Davenport thinks it was "unwise" to power the
primary end point to detect a 25% absolute treatment difference.
"If an agent improved results with that kind of effect, we
wouldn't need a trial to prove it; it would be obvious. Our own
figures at King's show a 10-15% improvement in jaundice
clearance and we limped across the statistical threshold on a
population of 153 infants," he said. That study was published in
the Journal of Hepatology in 2013.

Dr. Davenport said, "All three centers (in the UK) are very
pro-steroids . . . and have been for a long time. We at King's
were the last to hold out until we had performed our own
analyses and now are convinced of its value."